Pulmonary and systemic fluid filtration after continuous versus bolus interleukin-2 infusion

Interleukin-2 has been widely investigated as adjuvant therapy for advanced cancer and is administered by either bolus or continuous infusion. We compared the effects of bolus and continuous interleukin-2 infusion on pulmonary (QL) and systemic microvascular fluid filtration in 11 adult sheep prepared with chronic lung and soft-tissue lymph fistulas. Interleukin-2 was administered as a bolus infusion (100,000 units/kg) every 8 hours for 3 days or as a continuous infusion at the same dose for 3 days. No significant changes in pulmonary hydrostatic pressures or pulmonary vascular resistance were noted after either bolus or continuous interleukin-2 infusion. However, significantly decreased (p less than or equal to 0.05) systemic vascular resistances were observed in both groups. QL increased steadily throughout the infusion period in both groups, peaking at three times baseline on the third infusion day. The plasma/interstitial protein clearance (QL X lymph/plasma protein ratio) rose similarly in both groups, indicating increased barrier permeability. Increased lymphocyte clearance into lung lymph occurred by day 3 but was not associated with lymphocytic sequestration in the lung interstitium. We conclude that pulmonary and systemic microvascular fluid and protein flux exhibit similar changes after bolus or continuous interleukin-2 infusion. These changes are associated with increased clearance of lymphocytes into lung lymph that are not sequestered in the pulmonary interstitium after infusions of shorter duration.